کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
7265858 | 1472900 | 2010 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A new Nav1.7 sodium channel mutation I234T in a child with severe pain
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: A new Nav1.7 sodium channel mutation I234T in a child with severe pain A new Nav1.7 sodium channel mutation I234T in a child with severe pain](/preview/png/7265858.png)
چکیده انگلیسی
Dominant gain-of-function mutations that hyperpolarize activation of the Nav1.7 sodium channel have been linked to inherited erythromelalgia (IEM), a disorder characterized by severe pain and redness in the feet and hands in response to mild warmth. Pharmacotherapy remains largely ineffective for IEM patients with cooling and avoidance of triggers being the most reliable methods to relieve pain. We now report a 5Â year old patient with pain precipitated by warmth, together with redness in her hands and feet. Her pain episodes were first reported at 12Â months, and by the age of 15-16Â months were triggered by sitting as well as heat. Pain has been severe, inducing self-mutilation, with limited relief from drug treatment. Our analysis of the patient's genomic DNA identified a novel Nav1.7 mutation which replaces isoleucine 234 by threonine (I234T) within domain I/S4-S5 linker. Whole-cell voltage-clamp analysis shows a I234T-induced shift of â18Â mV in the voltage-dependence of activation, accelerated time-to-peak, slowed deactivation and enhanced responses to slow ramp depolarizations, together with a â21Â mV shift in the voltage-dependence of slow-inactivation. Our data show that I234T induces the largest activation shift for Nav1.7 mutations reported thus far. Although enhanced slow-inactivation may attenuate the gain-of-function of the I234T mutation, the shift in activation appears to be dominant, and is consistent with the severe pain symptoms reported in this patient.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pain - Volume 14, Issue 9, October 2010, Pages 944-950
Journal: European Journal of Pain - Volume 14, Issue 9, October 2010, Pages 944-950
نویسندگان
Hye-Sook Ahn, Sulayman D. Dib-Hajj, James J. Cox, Lynda Tyrrell, Frances V. Elmslie, Antonia A. Clarke, Joost P.H. Drenth, C. Geoffrey Woods, Stephen G. Waxman,